DESCRIPTION: Osteoporosis and depression are increasingly important health problems in the United States. Reports demonstrating lower bone mineral density and increase fracture risk in patients with depression as compared with those without depression suggest that BMD and depression are related. Whether depression is a risk factor for osteoporosis remains unclear and there are numerous hypotheses about the mechanism of such a potential association. One question involves whether the depression itself or the treatment might be a risk factor for osteoporosis. Recently functional serotonin transporters have been discovered in bone. The clinical implications of this finding are unknown. Serotonin transporters are known to play an important role in depression in that most pharmacologic anti-depressants including selective serotonin reuptake inhibitors (SSRIs) function by blocking this transporter. Thus the serotonin transporter provides a potential link between osteoporosis and depression and anti-depressant treatment. Understanding the impact of serotonin on bone development and loss is important because there are a large number of people treated for depression with medications that alter uptake of serotonin. The objective of this proposal to examine the associations between both clinical depression and treatment with selective serotonin reuptake antagonists (SSRIs) and bone density in humans, to explore the impact of SSRI use on bone turnover and to examine associations between serotonin transporter genotypes and bone mineral density. [unreadable] [unreadable] [unreadable]